This proposal is for a five-year renewal of the Alzheimer's Disease Research Center at the University of California at San Diego (UCSD) in consortium with the Salk Institute. The major objective of our ADRC is to enhance research into Alzheimer's disease (AD), a disorder which is a major disabling disease of the elderly accounting for half of nursing home admissions as well as increasing mortality rate and impacting severely upon families and caregivers. We have sought to enlist investigators and develop resources necessary to move forward in a significant way in the understanding of the pathogenesis and pathophysiology of AD with the ultimate goal of learning enough about the disease to be able to prevent or alter its clinical course, at the same time improving our understanding of the clinical diagnosis, course and the relationship of neuropsychological dysfunction to specific brain lesions. The ADRC provides a clinical and neuropathological resource based upon annual evaluations of a cohort of volunteers willing to participate in clinical research, subjects with Alzheimer's disease and related disorders and normal aged matched volunteers. The Clinical Core activity provides subjects for research and pilot projects and also permits study of clinical and neuropsychological changes during the course of AD; forms the base for development of cross- cultural studies of AD, specifically, Hispanic, Chinese and Finnish studies; enables participation in multicenter drug studies and national registries such as CERAD and THA; generates a well edited longitudinal data base. The Neuropathological Core provides a source of brain tissue of patients characterized clinically and neuropathologically for use in research projects. The ADRC provides a setting to facilitate research training of AD investigators and information transfer to the professional and lay communities through our mini-residency program, conferences and other educational activities. We foster interdisciplinary research activities through collaborations, seminars, feasibility and pilot projects. Our specific research projects in this renewal include investigations of the precursor protein for the Beta amyloid present in neuritic plaques (Research Project 1); the specific nature of the memory and other cognitive deficits in the Alzheimer process (Research Project 2); the quantitative anatomical study of Alzheimer brain in regard to neuronal populations in dementia (Research Project 3); and the effect of nerve growth factor as a potential therapeutic modality (Research Project 4); The UCSD ADRC fosters new research initiatives through pilot and feasibility projects which span disciplines from electronmicroscopy to electrophysiology, from clinical psychiatry to neuro-ophthalmology and which involve faculty at neighboring institutions in San Diego as well as at UCSD.